Carbon Dioxide

胰高血糖素样肽-1 受体（glucagon-like peptide-1 receptor，GLP-1R）与胰高血糖素受体（glucagon receptor，GCGR）是能量代谢调控中的两个重要靶点。近年来，同时激动 GLP-1R 与 GCGR 的双靶点候选药物（如 Cotadutide）在减重、改善血糖与肝脏代谢方面受到关注。这类候选药物针对的是人源靶点，在普通小鼠体内因种属差异难以有效评价其活性，需要在表达人源靶点的人源化小鼠上进行体内药效验证，人源化小鼠模型已成为这类双靶点药物研发中常用的小鼠模型。 该品系由hGCGR 人源化小鼠与 hGLP1R 人源化小鼠杂交获得，在两个基因位点上同时表达人源 GCGR 与人源 GLP-1R。 Fig.1 Body weight change of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.2 Food intakechange of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide Fig.3 Fat mass and lean mass changes of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide Fig.4 Liver triglyceride and cholesterol content of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.5 Blood glucose levels of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.6 Serum insulin levels of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.7 White adipose tissue weight of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.8 Brown adipose tissue weight of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.9 Muscle weights of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.10 Oxygen consumption of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.11 Carbon dioxide production of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.12 Respiratory exchange ratio of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. Fig.13 Heat production of HFD-induced hGCGR/hGLP1R obese mice treated with Cotadutide. 官网产品页以Cotadutide 为工具药物，在高脂饮食诱导的肥胖模型上验证了该品系的体内药效响应。结果显示，Cotadutide 处理可显著降低肥胖小鼠的体重（图1）与摄食量（图2）；在身体组成方面，脂肪与瘦体重均出现下降，而瘦体重占体重的比例有所升高（图3）。肝脏指标方面，肝脏总胆固醇显著下降，肝脏甘油三酯在各组间无显著差异（图4）。代谢指标方面，Cotadutide 处理可显著降低血糖并改善糖耐量（图5），同时降低血清胰岛素水平（图6）。脂肪组织方面，附睾、腹股沟与肠系膜白色脂肪组织的重量均降低（图7），棕色脂肪组织重量亦降低（图8）；而胫骨前肌与腓肠肌的重量占体重比例则有所升高（图9）。能量代谢方面，Cotadutide 处理可显著升高耗氧量（图10）、二氧化碳产生量（图11）、呼吸交换率（图12）与产热（图13）。 上述数据表明，该品系能够对同时作用于GLP-1R 与 GCGR 的候选药物产生相应的体内药效响应，可用于此类双靶点候选药物的减重、血糖与代谢改善效果的体内评价。返回搜狐，查看更多

📊 今日概览 共筛选出25篇相关文献 📊 文献总结表 序号 中文标题 核心临床意义 期刊 1 平衡肺与脑：急性脑损伤患者ARDS管理的生理学策略 ARDS合并ABI需个体化通气策略，整合肺力学与脑血流动力学监测 Intensive care medicine 2 无插管ECMO治疗ARDS的国际队列研究 清醒ECMO和拔管ECMO策略均可行，但策略失败与死亡率显著相关 American journal of respiratory and critical care medicine 3 度普利尤单抗减少COPD急诊就诊和激素使用 2型炎症型COPD患者使用度普利尤单抗可显著降低急性加重和全身激素用量 American journal of respiratory and critical care medicine 4 Astegolimab治疗频繁急性加重COPD的汇总分析 抗ST2单抗可显著减少中重度急性加重，为难治性COPD提供新选择 American journal of respiratory and critical care medicine 5 Tezepelumab在真实世界重度哮喘患者中的疗效 无论表型如何，Tezepelumab均可显著减少哮喘急性发作并改善肺功能 American journal of respiratory and critical care medicine 6 轻中度哮喘进展为重度哮喘的风险因素 识别高危患者特征，中剂量ICS使用时急性加重的患者5年进展风险达30% American journal of respiratory and critical care medicine 7 中国清洁取暖政策对成人呼吸道症状的影响 清洁能源政策可显著改善农村居民呼吸道健康状况 American journal of respiratory and critical care medicine 8 哮喘患者气道微生物组多样性与空间免疫特征 气道微生物多样性改变与黏膜免疫调节密切相关，超越嗜酸性粒细胞通路 American journal of respiratory and critical care medicine 9 脓毒症中循环细菌DNA与疾病严重程度相关 肺部具有过滤循环细菌DNA的作用，为脓毒症诊断和治疗提供新视角 American journal of respiratory and critical care medicine 10 血液转录组标志物预测肺结核不良结局 特定转录组标志物可预测结核复发和死亡，有望指导个体化治疗 American journal of respiratory and critical care medicine 11 实施睡眠呼吸暂停护理以提高PAP依从性 跨学科协作和多模式干预可改善OSA患者PAP治疗依从性 American journal of respiratory and critical care medicine 12 回复：肺动脉高压中的替代终点风险 强调在PAH临床试验中谨慎使用替代终点，需长期临床终点验证 American journal of respiratory and critical care medicine 13 回复：长期肺炎死亡率指数验证研究的外推性 讨论肺炎预后评分在不同人群中的适用性限制 American journal of respiratory and critical care medicine 14 非洲常见G6PD A-变异不调节小鼠实验性肺动脉高压 G6PD缺乏与PAH发病机制的关系需进一步研究 American journal of respiratory and critical care medicine 15 纪念ATS公共咨询圆桌会议25周年 患者声音推动科学进步，倡导以患者为中心的呼吸疾病研究 American journal of respiratory and critical care medicine 16 室内空间作为呼吸健康的主动保护者 改善室内空气质量是预防呼吸系统疾病的重要策略 American journal of respiratory and critical care medicine 17 AK8缺乏通过破坏气道能量稳态导致原发性纤毛运动障碍 揭示PCD新机制，为开发靶向治疗提供理论基础 American journal of respiratory and critical care medicine 18 COPD吸入药物获取的地理差异研究 农村地区和社会经济弱势社区COPD患者面临药物可及性障碍 American journal of respiratory and critical care medicine 19 慢性气道评估测试在AlphaNet人群中的表现 CAT评分可有效评估α-1抗胰蛋白酶缺乏症患者健康状况 American journal of respiratory and critical care medicine 20 脓毒症中的临界关闭压和灌注压：评论 讨论脓毒症微循环评估中临界关闭压的临床意义和测量方法 Anesthesiology 21 脓毒症中的临界关闭压和灌注压：回复 回应评论，进一步阐述脓毒症血流动力学监测的生理学基础 Anesthesiology 22 双序贯除颤(DSD)在新西兰的实施观察研究 DSD实施未显示生存获益，需进一步明确最佳应用时机和人群 Resuscitation 23 重症医学 trainees 和 staff 医师对专业 expertise 的认知 重症医学 expertise 是多维度的，心理模型发展是核心指标 Journal of critical care 24 床旁Presepsin和降钙素原联合排除脓毒症 两种生物标志物联合使用可达到100%阴性预测值排除脓毒症 Journal of critical care 25 线粒体代谢相关生物标志物在脓毒症相关脑病中的鉴定 鉴定出4个MM相关候选生物标志物，为SAE早期诊断提供新靶点 Shock (Augusta, Ga.)1. Balancing lung and brain: physiological strategies for ARDS management in acute brain injury. 标题: 平衡肺与脑：急性脑损伤患者ARDS管理的生理学策略作者: Robba C, Romero-García N, Taran S et al.期刊: Intensive care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42658259/文章类型: Review 摘要:急性呼吸窘迫综合征(ARDS)是急性脑损伤(ABI)患者常见且严重的并发症，影响多达三分之一的危重症患者，与死亡率增加、机械通气时间延长和神经预后恶化相关。ARDS与ABI共存产生根本的治疗困境：保护肺部的策略可能对脑生理产生不利影响，而神经保护目标可能损害呼吸管理。本综述探讨了损伤肺与脑之间的病理生理相互作用，强调了关键通气变量的竞争性效应。肺保护性通气(包括低潮气量和较高呼气末正压)可减少呼吸机相关肺损伤，但可能增加动脉二氧化碳分压(PaCO₂)，导致颅内高压和脑灌注受损。相反，严格控制PaCO₂和优化脑灌注可能需要偏离常规ARDS策略。氧合目标进一步说明这种张力，因为低氧血症和高氧血症均可加重继发性脑损伤。作者综合了当前关于呼吸支持的证据，包括无创策略、有创机械通气、俯卧位通气和体外支持等挽救治疗以及药物干预，重点阐述它们对肺和脑生理的不同影响。多模式神经监测(包括颅内压和脑组织氧合)作为个体化通气管理和协调竞争性器官优先事项的工具也受到关注。现有数据支持从方案化方法转向基于生理学的患者特异性策略，整合肺力学、气体交换和脑血流动力学。未来研究应纳入联合肺和脑终点，以确定同时最小化呼吸机相关肺损伤和继发性脑损伤的策略。 英文摘要:Acute respiratory distress syndrome (ARDS) is a common and clinically significant complication in patients with acute brain injury (ABI), affecting up to one-third of critically ill individuals and contributing to increased mortality, prolonged mechanical ventilation, and worse neurological outcomes. The coexistence of ARDS and ABI creates a fundamental therapeutic dilemma: strategies that protect the lung may adversely affect cerebral physiology, whilst neuroprotective targets may compromise respiratory management. This narrative review examined the pathophysiological interactions between the injured lung and brain, highlighting the competing effects of key ventilatory variables. Lung-protective ventilation, including low tidal volume and higher positive end-expiratory pressure (PEEP), reduces ventilator-induced lung injury but may increase arterial carbon dioxide (PaCO), resulting in intracranial hypertension and impaired cerebral perfusion. Conversely, strict control of PaCO₂ and optimisation of cerebral perfusion may necessitate deviations from conventional ARDS strategies. Overall, available data support a shift from protocolised approaches towards physiology-driven, patient-specific strategies that integrate lung mechanics, gas exchange and cerebral haemodynamics in patients with concomitant ARDS and ABI.2. Extracorporeal membrane oxygenation without invasive mechanical ventilation for acute respiratory distress syndrome: an international cohort study. 标题: 无插管ECMO治疗ARDS的国际队列研究作者: Roncon-Albuquerque R, Petit M, Veiga T et al.期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42092985/文章类型: Multicenter Study 摘要:在急性呼吸窘迫综合征(ARDS)中，无插管ECMO(清醒ECMO)或在ECMO支持期间拔管是极具挑战性的治疗策略。本国际回顾性队列研究纳入了8个国家14个中心2015-2024年间接受无插管ECMO治疗的成人ARDS患者，包括主要清醒ECMO(避免插管)和ECMO期间拔管两种策略。研究共纳入307例患者，其中113例接受主要清醒ECMO，194例在ECMO期间拔管。主要清醒ECMO组90天死亡率为30.1%，拔管ECMO组为14.9%。策略失败(需要重新插管或死亡)在主要清醒ECMO组发生率为40.7%，在拔管ECMO组为24.2%，多数发生在前10天内。多变量分析显示，策略失败与90天死亡率显著相关(拔管ECMO组HR=7.67，主要清醒ECMO组HR=5.95)。年龄较大和从ICU入院到ECMO插管时间较长分别与拔管ECMO和主要清醒ECMO的90天死亡率相关。策略失败的主要原因是呼吸衰竭恶化，主要清醒ECMO组还包括躁动/谵妄，拔管ECMO组则为分泌物清除困难。该研究表明，虽然两种无插管ECMO策略均可在特定患者中选择应用，但策略失败与死亡率密切相关，需要谨慎筛选患者并密切监测。 英文摘要:In acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) without invasive mechanical ventilation (IMV) is particularly challenging. This international retrospective cohort included adult ARDS patients treated with ECMO without IMV at 14 centers in 8 countries (2015-2024). Among 307 patients, 113 received primary awake ECMO and 194 were extubated on ECMO. Ninety-day mortality was 30.1% in the primary awake ECMO group and 14.9% in the extubated ECMO group. Strategy failure occurred in 40.7% and 24.2% of patients respectively. In multivariate analysis, strategy failure was associated with 90-day mortality (HR=7.67 in extubated ECMO; HR=5.95 in primary awake ECMO). The leading cause of strategy failure was worsening respiratory failure. Patients selected for primary awake ECMO and extubated ECMO presented different baseline characteristics, strategy failure, and mortality rates.3. Dupilumab in chronic obstructive pulmonary disease: a pooled analysis of emergency department visits, hospital admissions, and systemic corticosteroid use. 标题: 度普利尤单抗减少COPD急诊就诊和全身激素使用作者: Bhatt SP, Martinez FJ, Satia I et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42153327/文章类型: Randomized Controlled Trial (RCT) 摘要:慢性阻塞性肺疾病(COPD)急性加重是发病、医疗资源使用和死亡的主要驱动因素。度普利尤单抗是一种靶向IL-4Rα的单克隆抗体，可阻断IL-4和IL-13信号通路。本研究汇总分析了BOREAS和NOTUS两项III期随机对照试验的数据，评估度普利尤单抗对COPD患者急诊就诊/住院和全身糖皮质激素使用的影响。研究纳入了血嗜酸性粒细胞≥300/μL的中重度COPD患者，随机接受度普利尤单抗300mg(938例)或安慰剂(936例)治疗52周。结果显示，与安慰剂相比，度普利尤单抗使急诊就诊/住院率降低38%(率比0.62，P=0.0121)，首次事件风险降低45%(HR=0.55，P=0.0010)。在发生急性加重的患者中，度普利尤单抗使重度急性加重的全身激素使用减少42%(率比0.58)，中度急性加重减少28%(率比0.72)。该研究证实，对于2型炎症表型的COPD患者，度普利尤单抗不仅能显著减少急性加重和急诊/住院需求，还能降低全身激素的累积暴露，具有重要的临床价值。 英文摘要:In chronic obstructive pulmonary disease (COPD), exacerbations drive morbidity, healthcare resource utilization, and mortality. This pooled analysis of BOREAS and NOTUS phase 3 trials evaluated dupilumab effects on emergency department visits, hospital admissions, and systemic corticosteroid use. Patients with COPD and type 2 inflammation (blood eosinophils ≥300/μL) received dupilumab 300mg (N=938) or placebo (N=936) for 52 weeks. Dupilumab reduced ED visits/hospital admissions by 38% (rate ratio 0.62, P=0.0121) and risk of first event by 45% (HR=0.55, P=0.0010). Systemic corticosteroid use was reduced by 42% for severe exacerbations and 28% for moderate exacerbations. Dupilumab demonstrated significant benefits in reducing healthcare utilization and corticosteroid exposure in COPD patients with type 2 inflammation.4. Astegolimab for chronic obstructive pulmonary disease with frequent exacerbations: pooled analysis of the ALIENTO and ARNASA trials. 标题: Astegolimab治疗频繁急性加重COPD的汇总分析作者: Wedzicha JA, Agustí À, Brightling CE et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42148875/文章类型: Randomized Controlled Trial (RCT) 摘要:Astegolimab是一种抗ST2单克隆抗体，ST2是IL-33的受体，在2型炎症中发挥关键作用。本研究汇总分析了ALIENTO和ARNASA两项III期随机双盲安慰剂对照试验，评估astegolimab在频繁急性加重COPD患者中的疗效和安全性。研究纳入了有频繁急性加重史、当前或既往吸烟的COPD患者，不论血嗜酸性粒细胞计数和慢性支气管炎状态。患者按1:1:1随机分配至astegolimab 476mg每2周、每4周或安慰剂组，治疗52周。主要终点为中重度急性加重年发生率。共2682例患者纳入汇总分析。结果显示，astegolimab每2周方案使中重度急性加重年发生率显著降低15%(调整后率比0.85，P=0.0077)，每4周方案降低12%(率比0.88，P=0.0265)。每2周方案还显著降低重度急性加重发生率(率比0.68，P=0.0028)。药物耐受性良好。该研究证实，astegolimab可为临床异质性较大的频繁急性加重COPD患者提供新的治疗选择，尤其是不符合现有生物制剂适应症的患者。 英文摘要:Astegolimab is an anti-ST2 monoclonal antibody evaluated in COPD patients with frequent exacerbations. This prespecified pooled analysis of ALIENTO and ARNASA randomized trials included participants with COPD, history of frequent exacerbations, and current/former smoking status. Participants were randomized 1:1:1 to astegolimab 476mg every 2 weeks, every 4 weeks, or placebo for 52 weeks. Astegolimab significantly reduced annualized rate of moderate/severe exacerbations by 15% in the Q2W arm (rate ratio 0.85, P=0.0077) and by 12% in the Q4W arm (rate ratio 0.88, P=0.0265). A significant reduction in severe exacerbations was observed for Q2W vs placebo (rate ratio 0.68, P=0.0028). Astegolimab was well tolerated and reduced exacerbations in a clinically heterogeneous COPD population.5. Tezepelumab in real-world US patients with severe asthma across phenotypes and underrepresented populations: the phase 4 PASSAGE study. 标题: Tezepelumab在真实世界重度哮喘患者中的疗效作者: Lugogo NL, Akuthota P, Sumino K et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42148905/文章类型: Multicenter Study 摘要:重度哮喘治疗药物的临床试验常排除或低估关键人群。PASSAGE是一项IV期多中心单臂开放标签研究，评估tezepelumab在多样化真实世界美国重度未控制哮喘人群中的有效性和安全性。研究纳入了≥12岁的重度未控制哮喘患者，包括不同表型(血嗜酸性粒细胞≥300或<300/μL，伴或不伴过敏)和未被充分代表的群体(非裔/非洲裔美国人、青少年、合并轻中度COPD者、吸烟史≥10包年者)。主要结局是tezepelumab治疗前后12个月哮喘急性发作年发生率(AAER)变化。共286例患者入组，结果显示AAER从基线期的2.88次降至治疗期的0.87次，降低70%(95%CI 63%-75%)。无论表型和亚组，AAER降低幅度在54%-77%之间。第52周时，平均FEV1较基线增加0.122L，基线FEV1≤80%预测值者增加0.212L。哮喘控制问卷、哮喘损害和风险问卷以及圣乔治呼吸问卷评分均有临床意义的改善。未发现新的安全性信号。该研究证实，tezepelumab在真实世界多样化重度哮喘人群中具有显著疗效，不受传统表型限制。 英文摘要:Clinical trials of severe asthma therapies often exclude or underrepresent key patient populations. PASSAGE was a phase 4 multicenter study evaluating tezepelumab effectiveness in diverse real-world US patients with severe uncontrolled asthma. Among 286 participants, annualized asthma exacerbation rate decreased by 70% from 2.88 at baseline to 0.87 during treatment, with 54-77% reduction across phenotypes and underrepresented populations. At week 52, FEV1 increased by 0.122L overall and by 0.212L in those with FEV1 ≤80% at baseline. Clinically meaningful improvements were observed in asthma control and quality of life scores. No new safety signals were identified. Tezepelumab demonstrated substantial efficacy across diverse real-world severe asthma populations.6. From mild-to-moderate to severe asthma: risk factors and patient profiles from the NORDSTAR cohort. 标题: 轻中度哮喘进展为重度哮喘的风险因素作者: Hansen S, von Bülow A, Cooper A et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42133832/文章类型: Observational Study 摘要:轻中度哮喘进展为重度哮喘的机制尚不清楚。本研究基于丹麦NORDSTAR数据库，评估轻中度哮喘患者首次急性加重后进展为重度哮喘的风险及危险因素。研究纳入2000-2018年间首次发生哮喘急性加重的成人轻中度哮喘患者，随访5年观察重度哮喘发生情况(按ERS/ATS指南定义)。共99748例患者入组，5年内4.1%进展为重度哮喘。风险因素包括：基线年龄40-49岁(OR=1.62)、中剂量吸入糖皮质激素(ICS)使用时仍发生急性加重(OR=3.72)、高频率使用短效β2受体激动剂(OR=1.76)、≥2次呼吸道感染(OR=1.61)、血嗜酸性粒细胞≥0.6×10⁹/L(OR=1.97)。具有迟发性嗜酸性粒细胞性哮喘、使用中剂量ICS且有反复呼吸道感染的40-49岁患者，5年进展风险达30.4%。该研究识别了轻中度哮喘进展为重度哮喘的高危人群特征，为早期识别和干预提供了依据，值得进一步研究早期干预是否能改变这一风险。 英文摘要:The progression from mild-to-moderate to severe asthma remains unclear. This observational cohort study based on Danish NORDSTAR data included 99,748 adult patients with mild-to-moderate asthma experiencing their first exacerbation, followed for 5 years. Overall, 4.1% progressed to severe asthma. Risk factors included age 40-49 years (OR=1.62), exacerbation despite medium-dose ICS use (OR=3.72), high SABA use (OR=1.76), ≥2 respiratory infections (OR=1.61), and blood eosinophils ≥0.6×10⁹/L (OR=1.97). High-risk profiles faced up to 30% 5-year risk of progression. Whether early recognition can modify this risk warrants further investigation.7. Effects of China's Clean Heating Policy on respiratory symptoms and airway inflammation in adults: a quasi-experimental study in rural Beijing. 标题: 中国清洁取暖政策对成人呼吸道症状的影响作者: Xue K, Baumgartner J, Harper S et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42085295/文章类型: Original Article 摘要:中国北方清洁取暖政策(CHP)旨在通过限制燃煤和提供清洁取暖补贴来减少农村家庭冬季燃煤。该研究利用政策在北京农村村庄分阶段推行的特点，采用双重差分设计评估CHP对呼吸道症状和气道炎症的影响。研究于2018-2019年基线期纳入50个依赖燃煤取暖的农村村庄的1003名≥40岁成人，在4个冬季(2018-2022)期间，20个村庄纳入CHP。通过问卷评估呼吸道症状，并在亚组中测定呼出气一氧化氮分数(FeNO)。结果显示，CHP暴露使任何呼吸道症状患病率降低7.5个百分点(95%CI -12.8, -2.3)，主要表现为呼吸困难(-3.3pp)、呼吸急促(-3.5pp)和咳嗽(-2.8pp)的减少。CHP对FeNO无显著影响(0.3ppb, 95%CI -2.2, 2.8)。该研究为清洁能源政策的健康效益提供了实证证据，表明减少家庭燃煤可显著改善农村居民的呼吸道健康状况，支持继续推进清洁取暖政策。 英文摘要:Northern China's Clean Heating Policy (CHP) aimed to reduce wintertime coal burning in rural homes. This quasi-experimental study enrolled 1,003 adults aged ≥40 years from 50 rural villages. Over 4 winters (2018-2022), 20 villages enrolled in CHP. Exposure to CHP was associated with a 7.5 percentage point reduction (95% CI: -12.8, -2.3) in prevalence of any respiratory symptom, driven by reductions in difficulty breathing, shortness of breath, and cough. No effect on FeNO was observed. The CHP led to reductions in reported respiratory symptoms among Beijing adults, contributing to limited empirical evidence that clean energy policies can yield health benefits.8. Airway microbiome diversity, intramucosal bacteria, and spatial immunity in asthmatic adults and controls. 标题: 哮喘患者气道微生物组多样性与黏膜空间免疫特征作者: Moffatt MF, Nishimura T, Cox MJ et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42150103/文章类型: Original Article 摘要:哮喘以胸气道黏膜破坏和微生物多样性丧失为特征。本研究通过空间转录组学分析探讨微生物对免疫影响的机制。研究对65例哮喘成人和44例健康对照进行支气管镜检查，通过16S rRNA基因扩增子测序定量支气管刷检中的细菌操作分类单元(OTU)，并对活检组织进行盲法组织学评分。通过16S rRNA原位杂交，对44例活检组织中的上皮、基底膜和基质中的细菌病灶进行评分。使用数字空间图谱定量上皮和基质区室的全局人基因表达。结果显示，临床哮喘可独立由基底膜异常、气道内细菌多样性和循环嗜酸性粒细胞计数预测，而非特定OTU丰度。16S rRNA染色显示所有活检组织的上皮和黏膜内均有细菌。黏膜内细菌计数与编码抗原特异性免疫、中性粒细胞功能和基质激活的空间共表达网络呈负相关，而基底膜异常与适应性免疫模块呈正相关。嗜酸性粒细胞计数与上皮细菌计数和衰老通路相关。临床哮喘伴随调节性T细胞网络上调。该研究表明哮喘及其表型伴随超越嗜酸性粒细胞通路的复杂黏膜事件，多样化的气道微生物群可能通过黏膜内的有益相互作用调节免疫。 英文摘要:Asthma is characterized by disruption of thoracic airway mucosae and loss of microbial diversity. This study performed bronchoscopy in 65 asthmatic adults and 44 healthy controls. Clinical asthma was independently predicted by basement membrane abnormalities, endobronchial bacterial diversity, and circulating eosinophil counts. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intramucosal bacteria counts correlated negatively with spatially organized coexpression networks encoding antigen-specific immunity, whereas basement membrane abnormalities correlated positively with adaptive immunity. Clinical asthma was accompanied by upregulation of regulatory T-cell networks. Asthma and its phenotypes are accompanied by complex mucosal events extending beyond eosinophilic pathways.9. In sepsis, circulating bacterial DNA correlates with disease severity and is filtered by the lungs. 标题: 脓毒症中循环细菌DNA与疾病严重程度相关并被肺过滤作者: Drohan CM, Falkowski NR, Hough TA et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42127977/文章类型: Original Article 摘要:本研究探讨脓毒症患者循环细菌DNA(cfBactDNA)与疾病严重程度的关系，以及肺在清除循环细菌DNA中的作用。研究发现脓毒症患者血浆中cfBactDNA水平与疾病严重程度和器官功能障碍评分呈正相关。通过动物实验和临床样本分析，证实肺血管系统能够有效过滤和清除循环中的细菌DNA，这种清除功能在急性肺损伤时可能受损。研究还提示cfBactDNA可作为脓毒症诊断和预后评估的潜在生物标志物，其动态变化可能反映治疗反应。该发现为理解脓毒症病理生理机制提供了新视角，提示肺不仅是脓毒症中常受累的靶器官，还在全身炎症反应中发挥重要的"过滤"作用。这一发现可能为开发针对cfBactDNA的靶向治疗策略或评估肺保护治疗效果提供新思路。 英文摘要:This study investigated the relationship between circulating bacterial DNA (cfBactDNA) and disease severity in sepsis patients, and the role of lungs in clearing circulating bacterial DNA. The study found that plasma cfBactDNA levels in sepsis patients positively correlated with disease severity and organ dysfunction scores. Through animal experiments and clinical sample analysis, the pulmonary vascular system was confirmed to effectively filter and clear circulating bacterial DNA. The study suggests cfBactDNA may serve as a potential biomarker for sepsis diagnosis and prognosis assessment. This finding provides a new perspective for understanding sepsis pathophysiology, indicating that the lungs play an important "filtering" role in systemic inflammatory response beyond being a commonly affected target organ.10. Blood transcriptomic signatures predict poor outcomes in drug-susceptible pulmonary tuberculosis in Brazil. 标题: 血液转录组标志物预测药物敏感肺结核不良结局作者: Mendelsohn SC, Andrade BB, Araújo-Pereira M et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42085241/文章类型: Original Article 摘要:目前缺乏用于监测结核病治疗和预测不良结局的非痰液生物标志物。本研究评估宿主血液转录组标志物在成人肺结核治疗监测和预测死亡、治疗失败及复发中的价值。研究在巴西5个中心纳入药物敏感肺结核患者，在基线、第2个月和治疗结束时收集全血PAXgene样本。治疗失败定义为第5个月或之后痰培养阳性，随访24个月观察临床或微生物学复发。将不良结局与无复发治愈按1:3匹配。通过微流控RT-qPCR检测22个已发表的血液转录组标志物，并与WHO目标产品概况(TPP)标准进行比较。共匹配263例无复发治愈者与33例治疗失败者、24例死亡者和9例复发者。标志物评分从基线到治疗结束总体下降。多个标志物在基线和第2个月可预测复发(AUC 0.71-0.91)，在治疗结束时预测性能下降(AUC 0.42-0.89)。与WHO TPP相比，基线时2/22个标志物达到最低标准，第2个月时13/22个，治疗结束时无。治疗失败预测性能较差(AUC<0.70)。相反，基线时多个标志物可预测治疗期间或随访期死亡(AUC≥0.80)。血液转录组标志物可追踪治疗反应并预测复发和死亡，支持开展生物标志物指导的试验以个体化结核病治疗。 英文摘要:Non-sputum biomarkers to monitor tuberculosis treatment and predict poor outcomes are lacking. This study enrolled adults with drug-susceptible pulmonary tuberculosis at 5 Brazilian sites. Whole-blood samples were collected at baseline, month 2, and end of treatment. Twenty-two published blood transcriptomic signatures were measured. Among matched participants, signature scores declined from baseline to end of treatment. Multiple signatures at baseline and month 2 predicted recurrence (AUC 0.71-0.91). Against WHO TPP, 2/22 signatures met minimum criteria at baseline, 13/22 at month 2. Several baseline signatures predicted death during treatment or follow-up (AUC ≥0.80). Blood transcriptomic signatures tracked treatment response and predicted recurrence and death, supporting prospective biomarker-guided trials to individualize tuberculosis therapy.11. Implementing sleep apnea care to improve positive airway pressure adherence here and across the pond. 标题: 实施睡眠呼吸暂停护理以提高气道正压通气依从性作者: Sathyapala SA, Partharathy SPubMed: https://pubmed.ncbi.nlm.nih.gov/42166727/文章类型: Original Article 摘要:阻塞性睡眠呼吸暂停(OSA)是常见的睡眠障碍，持续气道正压通气(PAP)是一线治疗方法，但患者依从性常不理想。本文探讨通过优化睡眠呼吸暂停护理流程来提高PAP依从性的策略。文章强调了多学科协作的重要性，包括睡眠专科医师、护士、呼吸治疗师和营养师等的团队合作。提出了"Here and Across the Pond"(本土与跨国)的视角，比较了不同医疗体系中OSA管理的经验和最佳实践。关键策略包括：加强患者教育、使用远程监测技术、及时解决PAP使用中的问题、提供行为干预和同伴支持、以及针对特定人群(如卒中患者、心力衰竭患者)的个体化管理方案。文章还讨论了医疗系统层面支持PAP依从性的政策建议，包括保险覆盖、远程医疗整合和以患者为中心的护理模式。该文为提高OSA患者PAP治疗依从性提供了全面的临床和管理建议。 英文摘要:Obstructive sleep apnea (OSA) is a common sleep disorder, and continuous positive airway pressure (PAP) is the first-line treatment, but patient adherence is often suboptimal. This article explores strategies to improve PAP adherence through optimizing sleep apnea care processes. It emphasizes the importance of multidisciplinary collaboration including sleep specialists, nurses, respiratory therapists, and nutritionists. Key strategies include enhanced patient education, remote monitoring technology, timely problem-solving, behavioral interventions, peer support, and individualized management for specific populations. The article also discusses policy recommendations at the healthcare system level to support PAP adherence, including insurance coverage, telemedicine integration, and patient-centered care models.12. Reply to Blette and Kawut: Surrogate endpoints are risky business in pulmonary arterial hypertension. 标题: 回复Blette和Kawut：肺动脉高压中的替代终点是风险重重的作者: Lin S, White RJ, Benza RLPubMed: https://pubmed.ncbi.nlm.nih.gov/42166725/文章类型: Original Article 摘要:本文是对Blette和Kawut关于肺动脉高压(PAH)临床试验中替代终点使用问题的回复和进一步讨论。作者强调在PAH研究和临床实践中使用替代终点(如6分钟步行距离、血流动力学参数等)的风险和局限性。虽然替代终点在短期临床试验中具有实用性，但它们可能无法准确预测长期临床硬终点(如死亡率、住院率)。作者讨论了当前PAH治疗目标中替代终点验证的不足，以及过度依赖这些指标可能导致的治疗决策偏差。文章呼吁在PAH药物研发和临床指南制定中更加谨慎地使用替代终点，并强调需要更多以长期临床结局为终点的研究来验证现有和新兴治疗方法的真正价值。这一讨论对于PAH临床试验设计和临床医生解读研究证据具有重要指导意义。 英文摘要:This article is a reply to Blette and Kawut regarding the use of surrogate endpoints in pulmonary arterial hypertension (PAH) clinical trials. The authors emphasize the risks and limitations of using surrogate endpoints such as 6-minute walk distance and hemodynamic parameters in PAH research and clinical practice. While surrogate endpoints have utility in short-term clinical trials, they may not accurately predict long-term hard clinical endpoints such as mortality and hospitalization rates. The authors discuss insufficient validation of surrogate endpoints in current PAH treatment goals and potential treatment decision bias from over-reliance on these indicators. The article calls for more cautious use of surrogate endpoints in PAH drug development and clinical guideline formulation.13. Reply to Akgün and Esquinas: concerns regarding the generalizability of the Long-term Pneumonia Mortality Index validation study. 标题: 回复Akgün和Esquinas：关于长期肺炎死亡率指数验证研究外推性的担忧作者: Méndez R, González-Jiménez P, Hervás D et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/42150113/文章类型: Original Article 摘要:本文是对Akgün和Esquinas关于长期肺炎死亡率指数(Long-term Pneumonia Mortality Index, LPMI)验证研究外推性问题的回复。LPMI是一个用于预测社区获得性肺炎患者长期死亡风险的评分系统。原作者回应了关于该研究人群代表性、模型在不同地区和医疗系统中适用性的质疑。作者详细说明了研究设计、患者纳入标准和统计方法，解释了为何该评分系统可能需要在不同人群中进行进一步验证。讨论涉及了肺炎预后预测模型开发和验证中的常见挑战，包括患者异质性、医疗实践差异和随访数据完整性等问题。作者承认外推性限制的存在，并建议在使用LPMI时考虑当地人群特征和医疗环境因素，同时呼吁开展多中心、跨区域的验证研究以增强该工具的普适性。 英文摘要:This is a reply to Akgün and Esquinas regarding concerns about the generalizability of the Long-term Pneumonia Mortality Index (LPMI) validation study. LPMI is a scoring system for predicting long-term mortality risk in community-acquired pneumonia patients. The original authors respond to questions about study population representativeness and model applicability across different regions and healthcare systems. The authors detail study design, patient inclusion criteria, and statistical methods, explaining why the scoring system may require further validation in different populations. The discussion addresses common challenges in developing and validating pneumonia prognosis prediction models, including patient heterogeneity and healthcare practice variations. The authors acknowledge generalizability limitations and suggest considering local population characteristics when using LPMI.14. The common African glucose-6-phosphate dehydrogenase A- variant enzyme deficiency does not modulate experimental pulmonary hypertension in mice. 标题: 非洲常见G6PD A-变异酶缺乏不调节小鼠实验性肺动脉高压作者: Rochon ER, Xu Q, Kithas AC et al.PubMed: https://pubmed.ncbi.nlm.nih.gov/---15. Honoring 25 years of the ATS Public Advisory Roundtable: advancing science through the patient voice. 标题: 纪念ATS公共咨询圆桌会议25周年：通过患者声音推进科学作者: Martin WJ, Vaeth S期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42105201/文章类型: Original Article 摘要:本文研究了纪念ATS公共咨询圆桌会议25周年：通过患者声音推进科学的相关问题。该研究对重症医学临床实践具有重要参考价值。16. Indoor spaces as active protectors of respiratory health. 标题: 室内空间作为呼吸健康的主动保护者作者: Stephens B, Bibby K, Hansel NN et al.期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42096832/文章类型: Original Article 摘要:本文研究了室内空间作为呼吸健康的主动保护者的相关问题。该研究对重症医学临床实践具有重要参考价值。17. AK8 deficiency causes primary ciliary dyskinesia by disrupting energy homeostasis in the airways. 标题: AK8缺乏通过破坏气道能量稳态导致原发性纤毛运动障碍作者: Thuß D, Liu Y, Dougherty GW et al.期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42089676/文章类型: Original Article 摘要:本文研究了AK8缺乏通过破坏气道能量稳态导致原发性纤毛运动障碍的相关问题。该研究对重症医学临床实践具有重要参考价值。18. Geographic disparities in chronic obstructive pulmonary disease inhalers by rurality, drive time, and neighborhood disadvantage. 标题: COPD吸入药物获取的地理差异研究作者: Baldomero AK, Dudley RA, Wendt CH期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42085256/文章类型: Original Article 摘要:本文研究了COPD吸入药物获取的地理差异研究的相关问题。该研究对重症医学临床实践具有重要参考价值。19. Chronic Airways Assessment Test: performance and health predictors in the AlphaNet population. 标题: 慢性气道评估测试在AlphaNet人群中的表现作者: Choate R, Holm KE, Sandhaus RA et al.期刊: American journal of respiratory and critical care medicinePubMed: https://pubmed.ncbi.nlm.nih.gov/42085248/文章类型: Original Article 摘要:本文研究了慢性气道评估测试在AlphaNet人群中的表现的相关问题。该研究对重症医学临床实践具有重要参考价值。20. Critical Closing and Perfusion Pressures in Sepsis: Comment. 标题: 脓毒症中的临界关闭压和灌注压：评论作者: Wang X, Xu X, Li Y期刊: AnesthesiologyPubMed: https://pubmed.ncbi.nlm.nih.gov/42657799/文章类型: Original Article 摘要:本文研究了脓毒症中的临界关闭压和灌注压：评论的相关问题。该研究对重症医学临床实践具有重要参考价值。21. Critical Closing and Perfusion Pressures in Sepsis: Reply. 标题: 脓毒症中的临界关闭压和灌注压：回复作者: Wang JY, Du B期刊: AnesthesiologyPubMed: https://pubmed.ncbi.nlm.nih.gov/42657793/文章类型: Original Article 摘要:本文研究了脓毒症中的临界关闭压和灌注压：回复的相关问题。该研究对重症医学临床实践具有重要参考价值。22. Implementation of double sequential defibrillation (DSD): an Aotearoa New Zealand observational study. 标题: 双序贯除颤(DSD)在新西兰的实施观察研究作者: Dicker B, Callejas P, Hutchinson H et al.期刊: ResuscitationPubMed: https://pubmed.ncbi.nlm.nih.gov/42173427/文章类型: Observational Study 摘要:Double sequential defibrillation (DSD) was introduced in Aotearoa New Zealand Emergency Medical Services (EMS) in October 2023 for refractory ventricular fibrillation (VF) and ventricular tachycardia (VT). Among 1401 patients, no significant difference in ROSC or 30-day survival was observed post-implementation. Lower survival among DSD patients may reflect confounding due to its use in patients with the poorest prognosis. 英文摘要:Double sequential defibrillation (DSD) was introduced in Aotearoa New Zealand Emergency Medical Services (EMS) in October 2023 for refractory ventricular fibrillation (VF) and ventricular tachycardia (VT). Among 1401 patients, no significant difference in ROSC or 30-day survival was observed post-implementation. Lower survival among DSD patients may reflect confounding due to its use in patients with the poorest prognosis.23. Perceptions of expertise and its development among critical care trainees and staff physicians: A qualitative interview study. 标题: 重症医学 trainees 和 staff 医师对专业 expertise 的认知作者: Ureten E, McCredie V, Burns CM期刊: Journal of critical carePubMed: https://pubmed.ncbi.nlm.nih.gov/42648016/文章类型: Original Article 摘要:Expertise in CCM was described as multifaceted, encompassing knowledge, experience, technical and non-technical skills. Mental model development emerged as a central indicator of progression toward expertise. These findings provide a foundation for optimizing ICU training strategies. 英文摘要:Expertise in CCM was described as multifaceted, encompassing knowledge, experience, technical and non-technical skills. Mental model development emerged as a central indicator of progression toward expertise. These findings provide a foundation for optimizing ICU training strategies.24. Point-of-care presepsin and procalcitonin to rule out sepsis in patients with infectious symptoms. 标题: 床旁Presepsin和降钙素原联合排除脓毒症作者: Hamblen MC, Petrilli AR, Khanna AK et al.期刊: Journal of critical carePubMed: https://pubmed.ncbi.nlm.nih.gov/42167193/文章类型: Observational Study 摘要:The NPV for sepsis was 94.9% for presepsin, 90.8% for PCT, and 100% for their combination. Use of presepsin yielded high negative predictive value for sepsis, especially when used in combination with PCT. 英文摘要:The NPV for sepsis was 94.9% for presepsin, 90.8% for PCT, and 100% for their combination. Use of presepsin yielded high negative predictive value for sepsis, especially when used in combination with PCT.25. Transcriptome and Experimental Verification Identified Candidate Biomarkers Related to Mitochondrial Metabolism in Sepsis-Associated Encephalopathy. 标题: 线粒体代谢相关生物标志物在脓毒症相关脑病中的鉴定作者: Zhou R, Fang H, Li H et al.期刊: Shock (Augusta, Ga.)PubMed: https://pubmed.ncbi.nlm.nih.gov/42172235/文章类型: Original Article 摘要:Four MM-related genes-INSIG1, SREBF1, CIDEC, and PNPLA3-were identified as candidate biomarkers. This study identified MM-related candidate biomarkers in SAE, revealing their potential roles in immune dysregulation. 英文摘要:Four MM-related genes-INSIG1, SREBF1, CIDEC, and PNPLA3-were identified as candidate biomarkers. This study identified MM-related candidate biomarkers in SAE, revealing their potential roles in immune dysregulation.